Synthesis of fluoroalkyl-derivatised BINAP ligands

Article abstract of DOI:10.1016/S0040-4039(01)01835-4

Fluoroalkyl-derivatised R-BINAP ligands have been prepared, characterised and applied in the ruthenium-catalysed asymmetric hydrogenation of dimethyl itaconate.

Full text of DOI:10.1016/S0040-4039(01)01835-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8551–8553
Synthesis of fluoroalkyl-derivatised BINAP ligands
David J. Birdsall,a Eric G. Hope,a Alison M. Stuart,a,* Weiping Chen,b Yulai Hub and
Jianliang Xiaob
aDepartment of Chemistry, University of Leicester, Leicester LE1 7RH, UK
bLeverhulme Centre for Innovative Catalysis, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, UK
Received 9 July 2001; accepted 28 September 2001
Abstract—Fluoroalkyl-derivatised R-BINAP ligands have been prepared, characterised and applied in the ruthenium-catalysed
asymmetric hydrogenation of dimethyl itaconate. © 2001 Elsevier Science Ltd. All rights reserved.
The attachment of long perfluoroalkyl chains to con-
ventional ligand scaffolds has been widely utilised for
the synthesis of ligand systems and metal-based cata-
lysts compatible with supercritical CO2 (scCO2) and
fluorous solvents.1–6 However, there have been rela-
tively few reports on the application of perfluoroalky-
lated chiral ligand systems. Notable examples include
the epoxidation of alkenes with fluorous chiral salen
manganese complexes,7 the asymmetric alkylation of
aromatic aldehydes using fluorous BINOL titanium
alkoxides,8 the asymmetric protonation with a BINOL-
related perfluoroalkylated chiral diol9 in the fluorous
phase, and asymmetric hydroformylation in scCO2
using a perfluoroalkylated-BINAPHOS derivative.10
Although asymmetric hydrogenation with metal–
BINAP complexes is one of the most extensively used
reactions in synthesis, fluoroalkylated BINAP ligands
have not appeared in the literature. In the examples
above, the direct influence of the perfluoroalkyl sub-
stituents on the reactivity and enantioselectivity has not
been unequivocally established, since spacer units are
often incorporated into the ligands in an attempt to
ameliorate the powerful electron withdrawing influence
of the perfluoroalkyl substituents. However, we have
established from a comparison of derivatised and
underivatised ligands in the rhodium-catalysed hydro-
genation of styrene11 and Gladysz et al. from the varia-
tions in w(CO) with perfluoroalkyl-derivatised phos-
phine ligands in trans-[IrCl(CO)L2] (L=phosphine)12
and from basicity studies of perfluoroalkyl-derivatised
amines,13 that it is virtually impossible to completely
eliminate the electronic effect arising from incorpora-
tion of these fluorinated chains. Consequently, we
thought that it would be interesting to prepare
fluoroalkylated BINAP ligands that may find applica-
tions in asymmetric transformations in scCO2 and
fluorous solvents and allow the electronic effect of the
fluoroalkyl tails to be determined. We report herein the
synthesis of two fluoroalkylated BINAP ligands and a
preliminary evaluation of these ligands in asymmetric
hydrogenation in conventional organic solvents.
Our groups have recently developed two simple,
efficient routes to perfluoroalkylated aryl phosphi-
nes.14,15 The direct attachment of a C6F13 group to the
aryl ring is available via a copper-mediated cross cou-
pling reaction between a perfluoroalkyl iodide and an
aryl iodide or bromide,14,15a whilst the incorporation of
an additional C2H4 spacer group (i.e. attachment of a
C2H4C6F13 group) is possible via a Heck coupling of
aryl halides with CH2ꢀCHC6F13, followed by reduction
of the resultant double bond.15b We have applied both
of these methodologies to the derivation of the pro-
tected (R)-6,6%-dibromo-2,2%-dihydroxy-1,1%-binaphthyl
for the preparation of the fluoroalkylated BINAP lig-
ands 3 and 4 (Scheme 1). The copper-mediated
perfluoroalkylation of (R)-6,6%-dibromo-2,2%-diacetoxy-
1,1%-binaphthyl, derived from 6,6%-dibromo-1,1%-bi-2-
naphthol and acetic anhydride, with perfluorohexyl
iodide was performed in C6H5F–DMSO (1:1) at 80°C
for 72 h to give (R)-6,6%-bis(perfluorohexyl)-2,2%-diace-
toxy-1,1%-binaphthyl in 99% yield.16 Following hydroly-
sis the perfluoroalkylated (R)-binaphthol
1
was
obtained in 89% overall yield. The Heck reaction of
(R)-6,6%-dibromo-2,2%-dibenzyloxy-1,1%-binaphthyl with
1H,1H,2H-perfluoro-1-octene was completed in 24 h at
125°C.15c Following hydrogenation catalysed by Pd/C
Keywords: asymmetric hydrogenation; fluorous ponytails; ruthenium
catalysts.
* Corresponding author. Tel.: 0116 252 2136; fax: 0116 252 3789;
e-mail: amc17@le.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01835-4

8552
D. J. Birdsall et al. / Tetrahedron Letters 42 (2001) 8551–8553
Scheme 1. (i) Ac2O, Et3N, DMAP, DCM; (ii) C6F13I, Cu, bipy, DMSO, C6H5F, 80°C, 72 h; (iii) NaH, MeOH; (iv) (CF3SO2)2O,
py, DCM, 0°C, 4 h; (v) NiCl2(dppe), Ph2PH, DABCO, DMF, 110°C, 74 h; (vi) BnCl, K2CO3, acetone; (vii) CH2ꢀCHC6F13,
NaOAc, palladacycle, DMF, 125°C, 24 h; (viii) 10% Pd/C, EtOAc, H2 (30 bar), rt, 16 h.
to reduce the double bonds and deprotect at the same
time, the fluoroalkylated (R)-binaphthol 2 was obtained
in 86% overall yield. The phosphination of 1 and 2 was
conducted according to a literature method developed
for non-fluoroalkylated binaphthols. The perfluoro-
alkylated binaphthol 1 was treated with triflic anhy-
dride in the presence of a base17 to form the chiral
ditriflate, which was then reacted with diphenylphos-
phine, [NiCl2(dppe)] and DABCO18 to give the
perfluoroalkylated (R)-BINAP ligand 3 in 48% yield.19
The same reaction involving 2 led to the isolation of 4
in 85% yield. The higher yield with 2 is probably an
indication of the influence of the additional C2H4 units
on the P–C coupling step of the synthesis. The resultant
off-white solids were characterised by a combination of
elemental analysis and multinuclear NMR. The 19F
NMR spectra revealed the anticipated six mutually-
coupled multiplets and the 31P{1H} NMR spectra
revealed singlets at −13.5 and −15.4 ppm, respectively.
can be judged by the excellent ees obtained with the
three ligands and the lower conversion observed with
Ru-3. These results indicate that the electronic effects
arising from 6,6%-fluoroalkylation of BINAP only
impact on the hydrogenation activity of the Ru-BINAP
catalysts. Electronic effects have been shown to play an
important role in a number of asymmetric catalytic
reactions including hydrogenation.22
In conclusion, the synthesis of perfluoroalkylated-
derivatives of BINAP, potential ligands for asymmetric
catalysis in scCO2 and fluorous solvents, has been
achieved using established methodologies. The applica-
tion of these ligands in the ruthenium-catalysed hydro-
genation of dimethyl itaconate in methanol establishes
that fluorous ponytails can impose significant effects on
the hydrogenation activity (the more electron with-
drawing the ponytails the less active the catalysts), but
not on the enantioselectivity. We will report the scope
and application of these ligands for asymmetric induc-
tion in scCO2 in due course.
To test if the fluorous BINAP ligands 3 and 4 are
capable of asymmetric induction and if the CH2CH2
spacers are necessary for high activity and enantioselec-
tivity, we first carried out the asymmetric hydrogena-
tion of dimethyl itaconate in CH3OH. The catalysts
Ru-3 and Ru-4 were prepared from the reaction of
[RuCl2(benzene)]2 with 3 and 4 in DMF, respectively,
according to a method designed by Noyori.20 The
hydrogenation reaction was carried out at ambient
temperature under 20 bar H2 in CH3OH for 15 min
(substrate/catalyst=2000, 1.0 mmol of catalyst,20 2 mL
solvent). For comparison, the same hydrogenation was
also performed with Ru-(R)-BINAP. The conversions
with Ru-3, Ru-4 and Ru-(R)-BINAP were 42, 83 and
88%, respectively, while the ee values with the three
catalysts were 95.3, 95.7, and 95.4%, with the S enan-
tiomer dominating the product in each case.21 Clearly,
fluorous ponytails impose no detectable effects on the
enantioselectivity of prochiral olefins such as dimethyl
itaconate, but affect the rates of the hydrogenation, as
Acknowledgements
We would like to thank the EPSRC (D.J.B., W.C.,
Y.H.), The Royal Society (E.G.H., A.M.S.), the Lever-
hulme Centre for Innovative Catalysis and its Industrial
Partners (Synetix, Johnson Matthey, Air Products and
Syntroleum) (J.X.) for financial support.
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19. A typical procedure is given for (R)-6,6%-bis(perfluoro-
hexyl) - 2,2% - bis(diphenylphosphino) - 1,1% - binaphthyl: A
solution of NiCl2(dppe) (0.133 g 0.25 mmol) and Ph2PH
(0.58 g, 3.14 mmol) in DMF (50 ml) was heated to 100°C
for 30 min when DABCO (1.129 g, 10.0 mmol) and a
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2,2%-ditriflate-1,1%-binaphthyl (3.00 g, 2.51 mmol) were
added. The resulting green solution was stirred at 110°C
for 2 h before an additional portion of Ph2PH (0.58 g,
3.14 mmol) was added and the heating was continued for
a further 72 h. After cooling the reaction mixture to room
temperature, DMF was removed by distillation. The
resulting brown solid was stirred for 30 min in methanol
(30 ml), filtered, washed with methanol and dried in
vacuo before being recrystallised from DCM and
methanol (1.53 g, 48%). Anal. calcd for C56H30F26P2: C,
53.42; H, 2.38; found C, 52.76; H, 2.35%. 1H NMR
(CDCl3): l 6.65 (2H, d, J=8.9 Hz), 6.85 (2H, d, J=8.9
Hz), 7.02 (8H, m), 7.25 (12H, m), 7.59 (2H, d, J=8.5
Hz), 8.00 (2H, d, J=8.5 Hz), 8.10 (2H, s). 31P{1H} NMR
(CDCl3): l −13.5. 19F{1H} NMR (CDCl3): l −81.19 (6F,
m), −110.67 (4F, m), −121.79 (8F, m), −123.17 (4F, m),
−126.50 (4F, m). [h]D=+104 (benzene, c 0.1).
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16. A typical procedure is given for (R)-6,6%-bis(perfluoro-
hexyl)-2,2%-diacetyloxy-1,1%-binaphthyl: A mixture of (R)-
6,6%-dibromo-2,2%-diacetoxy-1,1%-binaphthyl (4.0 g, 7.57
mmol), perfluorohexyl iodide (10.13 g, 22.8 mmol), cop-
per powder (2.94 g, 45.4 mmol), 2,2%-bipyridine (0.240 g,
1.5 mmol), C6H5F (75 ml) and DMSO (75 ml) was stirred
for 72 h at 80°C. After cooling to room temperature, the
reaction mixture was diluted with water (200 ml) and
DCM (300 ml), and filtered. The organic layer was
separated, washed with water (5×100 ml), dried (MgSO4),
and evaporated under reduced pressure. The resulting
green solid was extracted using perfluoro-1,3-dimethylcy-
clohexane (50 ml) and the solvent removed in vacuo.
Azeotropic distillation from DCM yielded the title com-
pound as an off-white solid (7.60 g, 99%). 1H NMR
(CDCl3): l 1.90 (6H, s), 7.30 (2H, d, J=8.9 Hz), 7.45
(2H, d, J=8.9 Hz), 7.59 (2H, d, J=8.9 Hz), 8.15 (2H, d,
J=8.9 Hz), 8.25 (2H, bs). 19F{1H} NMR (CDCl3): l
−81.21 (6F, m), −110.67 (4F, m), −121.87 (8F, m),
−123.19 (4F, m), −126.54 (4F, m).
(R)-6,6%-Bis(1H,1H,2H,2H-perfluoro-1-octyl)-2,2%-bis-
(diphenylphosphino)-1,1%-binaphthyl was prepared simi-
larly in 85% yield. Anal. calcd for C60H38F26P2. CH2Cl2:
C, 52.33; H, 2.89; P, 4.42; found C, 52.81; H, 2.81; P,
1
4.87%. H NMR (CDCl3): l 2.37 (4H, m), 2.95 (4H, m)
6.68 (2H, d, J=8.9 Hz), 6.72 (2H, d, J=8.9 Hz), 7.10
(12H, m), 7.18 (8H, m), 7.41 (2H, d, J=8.5 Hz), 7.64
(2H, s), 7.83 (2H, d, J=8.5 Hz). 31P{1H} NMR (CDCl3):
l −15.4. 19F{1H} NMR (CDCl3): l −81.22 (6F, m),
−114.97 (4F, m), −122.27 (4F, m), −123.26 (4F, m),
−123.92 (4F, m), −126.52 (4F, m). [h]D=+169 (benzene, c
0.1).
20. Ru-3 and Ru-4 are probably structurally similar to
[RuCl2(BINAP)(DMF)2] or its polymeric form. For
details of preparation, see: Kitamura, M.; Tokunaga, M.;
Ohkuma, T.; Noyori, R. Tetrahedron Lett. 1991, 32,
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21. The ee values were determined by a Varian CP-3380 GC
equipped with a Chiraldex G-TA (40m×0.25mm) column
after passing the product through a short silica column.
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